Support is requested to continue a multidisciplinary program that was begun in 1993 under the auspices of a P2O from NINDS. Through the study of a variety of pathological states such as perinataI asphyxia, neonatal stroke and neonatal infection, patterns and mechanisms of ischemic neonatal brain injury will be elucidated. It is the hypothesis of this proposal that the integrity of the blood brain barrier, cerebral perfusion, excitatory amino acid release availability of neurotrophic factors and substrates of intermediary metabolism, are critically important factors in the pathogenesis of neonatal brain injury. Through an integration of human research and basic science research we plan to study the role of these factors in the pathogenesis of neonatal ischemic brain injury. Taking what we observe in the human condition, we will develop new animal models and techniques, as well as use existing animal models and tissue culture paradigms with established methodology to unravel mechanisms. Through continuous in situ monitoring of injury viaMRI/MRS and near infrared spectroscopy(NIRS), we will be better equipped to study these mechanisms and meet our ultimate goal of providing therapies in the nursery for ischemic brain injury. Each project is conceptually interrelated and utilizes the scientific core for a centralized facility for all experimental manipulations. The programs four projects are 1) MRI predictors of outcome after perinatal asphyxia in humans, 2) Fructose bisphosphate in asphyxial brain injury 3) Neurotrophins in neonatal hypoxic-ischemic brain injury and 4) Mediators of ischemic brain injury in neonatal meningitis. Through these varied approaches we will investigate the cellular, molecular and physiological mechanisms of hypoxia/ischemia in the developing nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
1P50NS035902-01A1
Application #
2591835
Study Section
Special Emphasis Panel (ZNS1-SRB-K (J1))
Program Officer
Spinella, Giovanna M
Project Start
1997-04-01
Project End
2002-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Peyvandi, Shabnam; Kim, Hosung; Lau, Joanne et al. (2018) The association between cardiac physiology, acquired brain injury, and postnatal brain growth in critical congenital heart disease. J Thorac Cardiovasc Surg 155:291-300.e3
van Velthoven, Cindy T; Dzietko, Mark; Wendland, Michael F et al. (2017) Mesenchymal stem cells attenuate MRI-identifiable injury, protect white matter, and improve long-term functional outcomes after neonatal focal stroke in rats. J Neurosci Res 95:1225-1236
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Gano, Dawn; Ho, Mai-Lan; Partridge, John Colin et al. (2016) Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns. J Pediatr 178:68-74
Larpthaveesarp, Amara; Georgevits, Margaret; Ferriero, Donna M et al. (2016) Delayed erythropoietin therapy improves histological and behavioral outcomes after transient neonatal stroke. Neurobiol Dis 93:57-63
Gano, Dawn; Andersen, Sarah K; Glass, Hannah C et al. (2015) Impaired cognitive performance in premature newborns with two or more surgeries prior to term-equivalent age. Pediatr Res 78:323-9
Gano, Dawn; Andersen, Sarah K; Partridge, J Colin et al. (2015) Diminished white matter injury over time in a cohort of premature newborns. J Pediatr 166:39-43
Titomanlio, Luigi; Fernández-López, David; Manganozzi, Lucilla et al. (2015) Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models. Pediatr Neurol 52:566-584

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